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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
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Optimized Quantitative Assessment of Enhancer RNA Stability in Mouse Embryonic Stem Cells
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Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.

Dong Wang1, Ivan Garcia-Bassets, Chris Benner

  • 1Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.

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|May 17, 2011
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Summary

Cell-lineage factors like FoxA1 control androgen receptor (AR) binding to enhancers. FoxA1 downregulation reprograms hormonal response by shifting AR to new enhancers, impacting prostate cancer progression.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Biology

Background:

  • Mammalian genomes contain thousands of transcriptional enhancers crucial for cell-type-specific gene expression.
  • The mechanisms by which enhancers mediate signal-dependent transcriptional responses are not fully understood.

Purpose of the Study:

  • To investigate how cell-lineage factors influence the activity of regulated transcription factors like the androgen receptor (AR).
  • To explore the role of FoxA1 in modulating AR binding to enhancers and its implications in prostate cancer.

Main Methods:

  • Global nuclear run-on sequencing (GRO-seq) to analyze enhancer activity and RNA production.
  • Analysis of androgen receptor (AR) binding dynamics in response to FoxA1 levels.

Main Results:

  • Cell-lineage factors, such as FoxA1, can both facilitate and restrict transcription factor binding to distinct enhancer classes.
  • Downregulation of FoxA1, a marker of poor prognosis in prostate tumors, causes a significant shift in AR binding to a different set of enhancers.
  • Evidence of functional enhancers producing enhancer-templated non-coding RNA (eRNA), with some classes activating gene expression without nucleosome remodeling.
  • Liganded AR appears to induce both transcription initiation and elongation.

Conclusions:

  • A substantial reservoir of active enhancers exists and can be dynamically regulated to generate alternative gene expression programs.
  • These findings provide insights into sequential gene expression events in development, differentiation, and disease progression, particularly in prostate cancer.
  • FoxA1's role in regulating AR enhancer engagement highlights a potential therapeutic vulnerability in advanced prostate tumors.